The prevalence of Type 2 diabetes is expected to reach 20%-30% by 2050. In the last 8 years, a new class of drugs, called incretin mimetics, has been used successfully for the treatment of the disease. Incretin mimetics (including exenatide) have a very short half-life requiring frequent subcutaneous self-injections. Such delivery can be invasive, painful, present safety issues, and impact the patient's attitude towards medication adherence. Maintaining peptide stability and enabling the sustained long-term delivery of exenatide are expected to improve compliance, convenience, safety, cost, and treatment success. The current long acting formulation of exenatide is for only 1 week and does not allow for the medication to be removed if needed. The goal of the proposed program is to develop a small non-mechanical (passive) subcutaneous implant (reservoir) which will be able to deliver consistent, therapeutic levels of stable exenatide over a period of at least 3 months. The implant body is made of titanium and it is implanted subcutaneously in the upper arm or abdomen via a trocar, with local anesthetic during a simple 15-minute in-office procedure, and without the need for any surgical sutures. The implanted reservoir is fitted at one end with a Nanopore membrane fabricated to contain pores with diameters that are approximately twofold larger than the hydrodynamic diameter of the selected drug molecule; such membrane architecture has been shown to result in zero-order release kinetics. The proposed delivery method will eliminate the need for daily or weekly self-injections. Benefits include medication adherence, patient convenience, improved safety and efficacy, and cost effective maintenance therapy. Furthermore, the system will allow healthcare providers to quickly remove the medication if needed, an important consideration, as this class of drugs has been associated with acute pancreatitis. The primary Phase I objectives of this program are to develop a stable formulation of exenatide, and validate that the selected nanopore membrane is not subject to biofouling when exposed to in-vivo conditions and is robust enough to advance into preclinical studies, product development, and clinical testing. Our proposed work will build on existing data regarding the stabilization of biologics as we attempt two approaches in developing a stable formulation of exenatide at body temperature. In addition to monitoring the stability and potency of the drug as part of our output assay, we will also select a Nanopore membrane suitable for the delivery of peptides in a zero-order fashion and test the performance of such membrane in vivo. The company has already received feedback from the FDA on its Nanopore technology for another molecule during a pre-IND meeting. Upon successful completion of the proposed study, the company will be ready to submit a Phase II application which will further advance the proposed product into the IND phase. Successful completion of Phase I will also allow us to potentially reduce the size of the device, extend its duration, and explore using the same technology for the delivery of other biologics.